Öcal BERKAN, Serdal ARSLAN, Erhan ATAHAN, Müslim GÜL, Nil ÖZBİLUM, Hasan BAŞÇİL

Ateroskleroz ile il-1α (interleukin-1α -889 c/t) gen polimorfizmi arasındaki ilişkinin araştırılması

Amaç. Genetik ve çevresel faktörler arasındaki ilişki sonucu ortaya çıkan kardiyovaskülerhastalıkların gelişiminde inflamasyon anahtar rol oynamaktadır. İnterlökin-1α (IL-1α) nınproinflamasyon regülasyonunda önemli rolü vardır. Bu çalışmada IL-1α-889 C/T polimorfizmi ileateroskleroz arasındaki ilişkinin araştırılması amaçlanmıştır. Yöntem. Bu çalışma popülasyonu117 hasta (Grup I) ve 117 sağlıklı (Grup II) bireyden oluşmuştur. Grup I ve Grup II deki bireyleringenomik DNAsı izole edildi. IL-1α genotipleri rastgele seçilen örneklerden direkt dizi analiziyapılarak doğrulandı. Bulgular. Grup I 78 erkek ve 39 kadın bireyden, Grup II ise 49 erkek ve 68kadın bireyden oluşmaktadır. Grup I bireylerin yaş ortalaması 61,06; Grup II bireylerin yaşortalaması ise 59,47dir. Grup Ide 43 bireyde, Grup IIde ise 28 bireyde yüksek kolesterol (totalkolesterol>200 mg/dL) bulundu. Grup Ide 62 bireyde, Grup IIde 51 bireyde sigara içiciliğibulundu. Grup Ide 81 bireyde yüksek tansiyon ( sistolik kan basıncı>140 mmHg ve/veyadiyastolik kan basıncı >90 mmHg), 42 bireyde diyabet, Grup IIde 32 bireyde yüksek tansiyon, 41bireyde diyabet bulundu. Aterosklerotik Grup Ide CC genotip taşıyan bireyler grubun %54,70ini,CT genotip taşıyan bireyler %35,04nü ve TT genotip taşıyan bireyler ise %10,25inioluşturmaktadır. Grup IIde ise bu oranlar CC genotip taşıyanlarda %59,82; CT genotiptaşıyanlarda %30,76 ve TT genotip taşıyanlarda %9,40 olarak saptanmıştır. IL-1α polimorfizmiiçin C allel frekansı Grup IIde %75,21 ve Grup Ide %72,22dir. T allel frekansı dağılımı GrupIIde %24,78 ve Grup Ide ise %27,77dir. Sonuç. Koroner Arter hastalığı olan Grup I ile, kontrolgrubu olan Grup II arasında yaş, cinsiyet dağılımı, hipertansiyon ve hiperkolesterolemi açısındanistatistiksel olarak anlamlı bir ilişki saptanmıştır. Grup I ile Grup II arasında IL-1α-889 C/T genpolimorfizmi açısından istatistiksel olarak anlamlı bir ilişki saptanmamıştır.

Ateroskleroz ile il-1α (interleukin-1α -889 c/t) gen p olimorf izmi arasındaki ilişkinin araştırılmasi

Aim. Atherosclerosis is regarded as a chronic inflammatory disease developing in response toinjury in the vessel wall. Inflammation plays a key role in the development of atherosclerosis.Interleukin-1α (IL-1α) has a critical role on regulation of proinflammation. The aim the study wasto assess the relationship between the IL-1α -889 C/T polymorphism and the atherosclerosis.Method. The study population was composed of 117 patients (Group I) and 117 healthy adults(Group II). Genomic DNA of case and control was extracted from blood leukocytes. IL-1αgenotype were further confirmed by direct sequencing of randomly selected samples. Results. 78male and 39 female individuals in the group I, 49 men and 68 women in Group II. The average ageof individuals in the Group I 61.06, the average age of individuals in the Group II 59.47 years old.The Group I 43 and the Group II were detected in 28 individuals with high cholesterol(totalcholesterol>200 mg/dL). 62 individuals in the Group I and 51 individuals in the Group II wassmoking. The Group I 81 individuals with high blood pressure(systolic blood pressure>140 mmHgand / or diastolic blood pressure>90 mmHg), 42 individuals with diabetes, the Group II 32individuals with high blood pressure, diabetes was found 41 individuals. In the atheroscleroticcoronary artery patients of %54.70 individuals carrying the CC genotype, %35.04 individualscarrying the CT genotype and %10.25 individuals carrying the TT genotype constitutes. In thehealty control group, %59.82 individuals carrying the CC genotype, %30.76 individuals carryingCT genotype and %9.40 individuals carrying TT genotype. IL-1α polymorphism of C allelefrequency is %75.21 in the Group II and %72.22 in the Group I. T allele freguency distribution of%24.78 in the Group II and %27.77 in the Group I. Conclusion. Those with coronary arterydisease group between the Group II age, sex distribution, hypertension and hypercholesterolemiawere found statistically significant relationship. There was no statistically significant differencebetween groups according to the IL-1α-889 C/T gene polymorphism.

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1. Zengin H. Ateroskleroz patogenezi J. Exp. Clin. Med 2012; 29:101-6.
2. Mallika V, Goswami B, Rajappa M. Atherosclerosis pathophysiology and the role of novel risk factors: A clinicobiochemical perspective. Angiology 2007; 58: 513-22.
3. Haverkate F, Thompson SG, Pyke SD, Gallimore JR, Pepys MB. Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Lancet 1997; 349: 462-6.
4. Borish L, Steinke JW. Cytokines and chemokines. J Allergy Clin Immunol 2003; 111: 460-75.
5. Lendon LC, Davies MJ, Born GVR, Richardson PD. Atherosclerotic plaque caps are locally weakened when macrophages density is increased. Atherosclerosis 1991; 87: 87-90.
6. Moreno PR, Falk E, Palacios IF, Newell JB, Fuster V, Fallon JT. Macrophage infiltration in Acute Coronary Syndromes. Circulation 1994; 90: 775-8.
7. Tsimikas S, Witztum JL. Measuring circulating oxidized Low-Density lipoprotein to evaluate coronary risk. Circulation 2001; 103: 1930-2.
8. Arend WP. The balance between IL-1 and IL-1 Ra in disease. Cytokine Growth Factor Rev 2002; 13: 323-40.
9. Clay FE, Cork MJ, Tarlow JK, Blakemore AI, Harrington CI. Interleukin-1 receptor antagonist gene polymorphism associated with lichen sclerosus. Human Genetics 1996; 94: 404-10.
10. Zheng Zhang, Li-Jun Liu, Chen Zhang, Yong-Peng Yu. Association between Interleukin-1 Gene Single Nucleotide Polymorphisms and Ischemic Stroke Classified by TOAST Criteria in the Han Population of Northern China. Biomed Res Int 2013: 961039.
11. Sambrook J, Fritsch EF, Maniatis T. Molecular Cloning: A laboratory manual. 2nd ed. N.Y. Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press 1989; 1659.
12. Onat A. Erişkinlerimizde kalp hastalakları prevalansi, yeni koroner olaylar ve kalpten ölüm sıklığı. TEKHARF (Türk erişkinlerinde kalp hastalığı ve risk faktörleri) 2009.
13. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001; 285: 2486-97.
14. Özkan Y, Koca SS, Gürsu F, Sonkaya E, Poyrazoğlu OK, Dönder E. Hiperlipidemik Hastalarda Atorvastatin Tedavisinin Serum Paraoksonaz-1 Düzeyine Etkisi. Fırat Tıp Dergisi 2004; 9: 123-6.
15. Tokgözoğulu L, Özer N. Ateroskleroz patogenezi. Özcan N. Koroner kalp hastalıkları. 1. Baskı. Ankara 1997; 129-63.
16. Gordon DJ, Probstfeld JL, Garrison RJ. High-density lipoprotein cholesterol and cardiovascular disase: Four prospective American study. Circulation 1989; 37: 47-53.
17. Algün E, Şekeroğlu R, Erkoç R, Özbek H, Alcı S, İlhan M ve ark. Sigara İçen Sağlıklı Gönüllülerde Çeşitli Aterosklerotik Risk Faktörlerinin Araştırılması ve Düşük Doz ACE İnhibitörü Kullanımının Bu Parametreler Üzerine Etkisi. Van Tıp Dergisi 1999; 6: 10-4.
18. Franklin SS, Gustin W, Wong ND. Hemodynamic patterns of age related changes in blood pressure. The Framingham Heart Study.Circulation 1997; 96: 308-15.
19. DECODE Study Group. Glucose tolerance and mortality: Comparison of WHO and American Diabetes Association diagnostic criteria and European Diabetes Epidemiology Group. Lancet 1999; 354: 617-21.
20. Kishimoto T. Interleukin-6: discovery of a pleiotropic cytokine. Arthritis Res Ther 2006; 8: 2.
21. Kishimoto T. The biology of interleukin-6. Blood 1989; 74: 1-10.
22. Ikonomidis I, Andreotti F, Economou E, Stefanadis C, Toutouzas P, Nihoyannopoulos P. Increased proinflammatory cytokines in patients with chronic stable anjina and their reduction by aspirin. Circulation 1999; 100: 793-8.
23. Frostegård J, Ulfgren AK, Nyberg P, Hedin U, Swedenborg J, Andersson U. ve ark. Cytokine expression in advanced human atherosclerotic plaques: Dominance of proinflammatory (Th1) and macrophage stimulating cytokines. Atherosclerosis 1999; 145: 33-43.
24. Uyemura K, Demer LL, Castle SC, Jullien D, Berliner JA, Gately MK ve ark Cross-regulatory roles of interleukin (IL)-12 and IL-10 in atherosclerosis. J Clin Invest 1996; 97: 2130-8.
25. Woods A, Brull DJ, Humphries SE, Montgomery HE. Genetics of inflammation and risk of coronary artery disease: The central role of interleukin-6. Eur Heart J 2000; 21: 1574-83.
26. Francis SE, Camp NJ, Burton AJ, Dewberry RM, Gunn J, Stephens-Lloyd A. ve ark.Interleukin -1 receptor antagonist gene polymorphism and coronary artery disease. Circulation 1999; 99: 861-6.
27. Kastrati A, Koch W, Berger PB, Mehilli J, Stephenson K, Neumann FJ et al. Protective role against restenosis from an interleukin -1 receptor antagonist gene polymorphism in patients treated with coronary stenting. J Am Coll Cardiol 2000; 362168-73.
28. Shimada K, Watanabe Y, Mokuno H, Iwama Y, Daida H, Yamaguchi H. Common polymorphism in the promoter of the CD14 monocyte receptor gene is associated with acute myocardial infarction in Japanese men. Am J Cardiol 2000; 86: 682-4.
29. Francis SE, Camp NJ, Burton AJ, Dewberry RM, Gunn J, Stephens- Lloyd A et al. IL-1Ra gene polimorphism and restenosis after coronary angioplasty. Heart 2001; 86: 336-40.
30. Vohnout B, Di Castelnuovo A, Trotta R, DOrazi A, Panniteri G, Montali A et al. IL-1 gene cluster polimorphisms and risk of coronary artery disease. Haematologica 2003; 88: 54-60.
31. Banerje I, Pandey U, Hasan O, Parihar R. Association between inflammatory gene polymorphismsand coronary artery disease in an Indian population. J Thromb Thrombolysis 2009; 27: 88-94.